The present invention relates to the field of drug delivery. More particularly, this invention relates to a method of stimulating neurological tissue as part of a prosthetic device.
There are several types of prosthetic devices used for stimulation of neural tissue or neurons. There are visual prostheses used to artificially restore vision in blind patients, which are currently being developed, and auditory prostheses used to artificially restore hearing. Currently, the method used to stimulate neural tissue associated with the visual and auditory systems includes developing devices and software for the application of electrical current to neural tissue. The basis of this technology was established in the late 1960s by Brindley who implanted arrays of surface stimulation electrodes in human visual cortical to generate the perception of multiple light flashes. These perceptions, called phophenes, can be arranged in a spatially organized manner so as to produce a primitive form of patterned vision. All implants under current development in these laboratories are designed to convert an electrical image into a patterned series of electrical impulses that, through a specially designed electrode array, will deliver current to the neural tissue to produce a visual perception. Currently, a cortical implant, which involves the placement of an electrode array in contact with the visual cortex, is being developed by a number of groups, worldwide. In addition, a retinal implant, which involves an electrode array placed either in front of (epiretinal) or beneath (sub-retinal) the retinal tissue is also being developed by a number of groups, worldwide. These electrode arrays are designed to deliver electrical impulses to stimulate currents to the retina in a spatially organized manner so as to produce visual perceptions through phophenes.
Electrode arrays have certain problems that lead to technical difficulties. Among the technical difficulties are that electrode arrays are not necessarily biocompatible. Electrode arrays are comprised of metal and often present the complication of oxidation at their termini. Electrode breakdown may result when metal atoms are deposited in tissues as the result of electrical current passage through electrodes placed in conducting body-fluid media. This may result in tissue toxicity as well as functional degradation of electrode performance. Increased electrical current may then become necessary to elicit the perception of phosphenes. This can lead to further tissue toxicity as a result of increased heat production at the electrode/tissue interface. In addition, from a physiological standpoint, electrical current lacks specificity with regard to the cell types it stimulates.
Formed vision requires the appropriate stimulation of ON and OFF channels of the visual system. These channels are established within the retina, very early in the process of visual perception to define the borders of objects. When light strikes a photoreceptor, chemical signals are transmitted to ON-bipolar and OFF-bipolar cells. ON-bipolar cells increase the release of chemical neurotransmitters when their corresponding photoreceptors receive a light stimulus and decrease this release when light is withdrawn. OFF-bipolar cells decrease the release of chemical neurotransmitters when their corresponding photoreceptors receive a light stimulus and increase the release of chemical neurotransmitter when light is absent or withdrawn. These ON and OFF bipolar cells communicate with ON and OFF retinal ganglion cells. The retinal ganglion cells are the output cells of the retina, which act through neurotransmitter synapses. In this way, the retina establishes the edges of objects through chemically encoded messages by measuring the contrast between adjacent points within the visual world. Thus, when stimulating the retina for the purpose of prosthetic vision in patients who have lost their photoreceptors, both ON-center and OFF-center bipolar and ganglion cells must be stimulated in an appropriate manner, according to local regions of bright and dark within the visual scene.
The visual prostheses used to artificially restore vision in blind patients which are currently being developed use electrical current to stimulate the ON-center and OFF-center bipolar and ganglion cells. Electrical current, however is non-specific regarding the cell types stimulated. Thus, both ON-center and OFF-center cells are stimulated, simultaneously. This results in a loss of edge information. Consequently, the patient perceives an often amorphous bright or dark spot or banana shaped area of light called a phosphene. Current technology has demonstrated that the objects or shapes perceived by experimental test subjects often do not correlate with the intended stimulus pattern.
The perception is often not consistent with the spatial organization on the electrode array. The axon belonging to a cell is typically remote from the cell body (soma) or dendrites. The soma and dendritic portions of the cell represent the inputs of a neuron, while the axon is a signaling output structure. Electrical stimulation stimulates the retinal axons, such as the nerve fiber layer or the retinal ganglion cell axon, in addition to the dendrites and soma. The result is that the spatial organization of the electrode will not be spatially transferred to the cells. The electrode array is used to form pixels for stimulating the cells; however, when this is done, the spatial relation of the pixels will not be transferred directly to the cells that need stimulation for the prosthesis. The pixels will be displaced since the axons are typically remotely located from the center of the cell. In other words, a stimulation a single axon, or an axon bundle, will result in an unpredictable perception that is not spatially related to the intended site of stimulation.
What is needed is a method and apparatus for stimulation of cells. What is also needed is a method and apparatus that can be used to precisely stimulate certain cells. What is also needed is method for stimulating neural tissue to produce a predictable perception when spatial relation is needed. What is further needed is an implantable device that is biocompatible and that will remain biocompatible.
A drug delivery system includes a plurality of sites, a fluid channel for delivering a drug to one of the plurality sites, and a light channel for delivering light to an area near one of the plurality of sites. The fluid channel is a micro fluidic channel and the light channel is a wave-guide. The light channel may also be a fiber optic cable. At least a portion of the drug delivery system is housed on a chip. In the chip the light channel intersects the fluid channel. The chip further includes a major surface, and a minor surface. The plurality of sites are on the major surface. The fluid channel is adapted to deliver fluid to a site on the major surface. The light channel directs light at the fluid channel wherein light from the light channel does not substantially exit to the major surface. The drug delivery system also includes a light source operatively connected to the light channel and a pump in fluid communication with the fluid channel.
In one embodiment, the drug delivery system includes a digital light processor, which receives an input. The digital light processor outputs light in response to the input. In other embodiments, the drug delivery system includes electrodes positioned near a site. The drug delivery system selectively delivers drugs to various types of neurologic cells including those associated with the eyes, the ears, and spine as well as basal ganglion, and hypothalamus.
In operation a solution of a photoactivatable caged neuro-active pro-drug is delivered to a preselected area in-vivo and photolytically activated in the solution at the preselected area. The neuro-active pro-drug could be an antagonist or agonist of neuronal activity. More than one photolytically activated molecule could be placed in the solution.
Advantageously, the method and apparatus stimulates cells at the cell center (soma or dendrites) to precisely stimulate certain cells. This method and apparatus stimulates the neural tissue and produces a predictable perception when spatial relation is needed. A further advantage is that the resulting implantable device is biocompatible and remains biocompatible.